The proposed research aims to clarify the relationship between the major histo-compatibility gene complex, HLA, and Dementia of the Alzheimer Type (DAT). Previous research has indicated that genetic and immunological factors are involved in DAT and that the HLA gene complex is related to immunological mechanisms and various neurological diseases of unknown origin. These studies led to preliminary research on the association between HLA typing and DAT. Although together the studies of DAT/HLA associations suggest a relationship between specific HLA antigens and DAT, some of the results are conflicting. Methodological difficulties may explain the discrepancies; for example patients with both dementia and depression (another psychiatric illness related to the HLA gene complex) are generally not segregated out or even identified. The proposed research will, therefore, investigate HLA typing in four groups of subjects as carefully defined as the state of the art permits: (1) patients with DAT; (2) patients with DAT and concurrent symptoms compatible with Major Depressive Disorder; (3) patients with Major Depressive Disorder alone; and (4) matched controls. In addition, first-degree relatives, when available, will be studied. A substantial number of subjects (group 2) will show features of both cognitive deficit and depression. Because no large-scale longitudinal studies have yet clarified these kinds of patients with overlapping symptoms, neuropsychological and psychosocial profiles will be collected to improve our understanding and clinical descriptions of such patients. The cause or causes of DAT remain(s) unknown; most likely they are multiple. The presence of HLA/DAT associations may be useful in distinguishing homogeneous subgroups among patients with DAT, homogeneity which could be of inestimable value with respect to treatment, outcome, and prediction of risk in as yet unaffected individuals. HLA associations with particular subgroups of patients with DAT offers, therefore, the possibility of refining our definition of a relatively global and heterogeneous syndrome into more specific disease entities.